Ovarian cancer is the deadliest gynecological malignancy, contributing to poor overall survival rates. Our previous study suggested that lipopolysaccharide (LPS) might reduce peritoneal dissemination of ovarian cancer by enhancing cytotoxic-associated innate immunogenicity. In this study, we explored the potential cytotoxic effects of different LPS chemotypes as a novel therapeutic approach for ovarian cancer. LPS-induced chemokines are toll-like receptor 4 (TLR4)-dependent and high TLR4 levels are correlated with improved overall survival outcomes. LPS did not directly impact ovarian cancer cell proliferation. Notably, LPS chemotypes, particularly lipid A, similarly modulated chemokine expression and induced cytotoxicity of peripheral blood mononuclear cells (PBMCs) to ovarian cancer cells, highlighting the critical role of lipid A component in LPS structure. Monophosphoryl lipid A (MPLA), a detoxified derivative of LPS commonly used as a vaccine adjuvant, exhibited similar cytotoxicity of PBMC when compared to LPS and induced CCL5 and CXCL8 in PBMCs. Treatment with MPLA significantly increased survival rates in the peritoneal dissemination model of ovarian cancer, reducing tumor burden and ascites. In conclusion, detoxified lipid A derivatives, such as MPLA, appear as a promising LPS-based immunotherapeutic candidate to enhance immune cell-mediated cytotoxicity for the treatment of ovarian cancer.

Breast cancer is the second leading cause of cancer death in women. Since cancer disrupts immune checkpoints to suppress the anti-tumor response, we assessed immune checkpoint signatures linked with NK and T cells in breast cancer including triple-negative breast cancer (TNBC) subtypes. Furthermore, critical immune checkpoints related to overall survival were identified using the in-silico and comparative analysis. Immune checkpoint signatures were breast cancer subtype-specific, showing differential signature in each subtype. High levels of immune checkpoints were related to overall survival in some breast cancer subtypes. The differential overall survival rates of breast cancer subtypes may be due to the final net balance of total immune checkpoints by exerting either inhibitory or stimulatory interaction with immune cells. Critical immune checkpoints for poor overall survival of breast cancer subtypes are as follows: UL16 binding protein 2 (ULBP2) in both basal-like breast cancers and basal-like 2 TNBC subtype; V-set domain containing T cell activation inhibitor 1 (VTCN1) in immunomodulatory TNBC subtype. In conclusion, specific immune checkpoints may differentially influence overall survival in a breast cancer subtype-specific manner.

Stroke is the second leading cause of death and a major cause of long-term disability worldwide. Within minutes of onset, cerebral ischemia triggers a cascade of pathophysiological events that ultimately result in irreversible tissue damage. Post-ischemic inflammation plays a critical role in cerebral ischemia-reperfusion injury, characterized by the elevated release of cytokines and chemokines. Interleukin (IL)-32 is known to induce several cytokines, particularly pro-inflammatory ones such as IL-6, tumor necrosis factor (TNF)-α, and IL-1β. Targeting inflammatory pathways are of great interest in stroke research. In this study, we investigated the role of IL-32γ in a middle cerebral artery occlusion (MCAO) model using transgenic (TG) mice expressing human IL-32γ. Compared to wild-type (WT) mice, IL-32γ TG mice exhibited a significantly reduced infarct volume after MCAO. Accompanying the decreased brain tissue damage, the levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β were markedly lower in IL-32γ TG mice than in WT controls. These findings suggest that IL-32γ attenuates the inflammatory response in ischemic brain injury. Specifically, IL-32γ reduced the expression of pro-inflammatory cytokines and the number of apoptotic cells following ischemic insult. In conclusion, our results demonstrate that IL-32γ protects the neuroinflammatory response in brain injury and may serve as a potential neuroprotective therapeutic target.

This review examines the effects of simulated microgravity on cancer cells and their response to anticancer drugs. In the unique environment of space, characterized by near-weightlessness, biological systems function differently compared to Earth’s normal gravitational conditions, potentially altering drug efficacy. As human space exploration advances, understanding pharmaceutical behavior in microgravity becomes essential for astronaut healthcare. We present comprehensive findings on how microgravity conditions, simulated using technologies such as the Rotary Cell Culture System and 3D clinostats, affect cancer cell behavior and drug sensitivity. The review analyzes how microgravity influences anticancer drug effectiveness, with evidence suggesting increased drug sensitivity in certain cancer types through mechanisms involving membrane property alterations, drug transport modifications, and signaling pathway changes. We discuss key experimental findings across various cancer models, including leukemia, gastric, ovarian, and colorectal cancers, while addressing methodological limitations of microgravity simulation research. This synthesis of current knowledge advances our understanding of cancer treatment in space environments and may offer novel insights for terrestrial therapeutic strategies.

Herbal medicinal products are gaining attention due to their accessibility and relative safety, yet challenges such as inconsistent efficacy and potential cytotoxicity remain. In this study, to overcome these limitations, we applied a plasma-based ionization method to a combination of Perilla frutescens and Taraxacum platycarpum Dahlst and evaluated its biological effects. THP-1 and Raw 264.7 cells were treated with either ionized or non-ionized extracts, followed by assessments of cell morphology, confluency, viability, and pro-inflammatory cytokine production. Ionization effectively reduced cytotoxic effects, as evidenced by preserved normal cell morphology and viability, and the absence of elevated proinflammatory cytokines. Notably, non-ionized extracts alone induced significant levels of pro-inflammatory cytokines in both cell types, suggesting a potential risk of undesirable immune activation. Although anti-inflammatory activity was not significantly enhanced, it was maintained in Raw 264.7 cells. In THP-1 cells, the ionized extract showed a trend toward enhanced anti-inflammatory activity, with reduced variability compared to the non-ionized extract. These findings suggest that plasma-based ionization may stabilize and improve the reliability of herbal extract efficacy without introducing adverse effects.

Peroxiredoxin-6 (PRDX6) is an oxidative stress response protein with multiple roles under reactive oxygen species (ROS)-mediated conditions. The multifunctional cytoprotective role of the protein PRDX6 is to maintain cellular homeostasis and membrane integrity through intracellular ROS and phospholipid turnover. The PRDX6 promoter region has been reported in several biological regulations because of its key binding sites. However, the human PRDX6 promoter sequence is not yet fully understood. In this study, we discovered and characterized the proximal promoter sequence of human PRDX6. Interestingly, the identified human PRDX6 promoter was about 1 kb shorter than the one reported in the database. Further studies with the new human PRDX6 promoter analysis will help to understand intracellular ROS and phospholipid turnover to maintain cellular homeostasis. This report provides the human PRDX6 proximal promoter sequence.